Implications of SARS-CoV-2 genetic diversity and mutations on pathogenicity of the COVID-19 and biomedical interventions

Abdullahi, Idris Nasir; Emeribe, Anthony Uchenna; Ajayi, Onaoluwa A.; Oderinde, Bamidele Soji; Amadu, Dele Ohinoyi; Osuji, Ahaneku Iherue

doi:10.1016/j.jtumed.2020.06.005

Cited by 52 publications

(60 citation statements)

References 38 publications

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“…Mutation studies also help track changes in the infectivity and virulence of mutants, reveal new strains with possible implications on immune escape and provide important clinicoepidemiological data (Abdullahi et al, 2020;Pachetti et al, 2020;Xi et al, 2020;Zou et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Mutation Landscape of SARS COV2 in Africa

Nassir¹,

Musanabaganwa

Mwikarago

2020

Preprint

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COVID-19 disease has had a relatively less severe impact in Africa. To understand the role of SARS CoV2 mutations on COVID-19 disease in Africa, we analysed 282 complete nucleotide sequences from African isolates deposited in the NCBI Virus Database. Sequences were aligned against the prototype Wuhan sequence (GenBank accession: NC_045512.2) in BWA v. 0.7.17. SAM and BAM files were created, sorted and indexed in SAMtools v. 1.10 and marked for duplicates using Picard v. 2.23.4. Variants were called with mpileup in BCFtools v. 1.11. Phylograms were created using Mr. Bayes v 3.2.6. A total of 2,349 single nucleotide polymorphism (SNP) profiles across 294 sites were identified. Clades associated with severe disease in the United States, France, Italy, and Brazil had low frequencies in Africa (L84S=2.5%, L3606F=1.4%, L3606F/V378I/=0.35, G251V=2%). Sub Saharan Africa (SSA) accounted for only 3% of P323L and 4% of Q57H mutations in Africa. Comparatively low infections in SSA were attributed to the low frequency of the D614G clade in earlier samples (25% vs 67% global). Higher disease burden occurred in countries with higher D614G frequencies (Egypt=98%, Morocco=90%, Tunisia=52%, South Africa) with D614G as the first confirmed case. V367F, D364Y, V483A and G476S mutations associated with efficient ACE2 receptor binding and severe disease were not observed in Africa. 95% of all RdRp mutations were deaminations leading to CpG depletion and possible attenuation of virulence. More genomic and experimental studies are needed to increase our understanding of the temporal evolution of the virus in Africa, clarify our findings, and reveal hot spots that may undermine successful therapeutic and vaccine interventions.

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Section: Introductionmentioning

confidence: 99%

Mutation Landscape of SARS COV2 in Africa

Nassir¹,

Musanabaganwa

Mwikarago

2020

Preprint

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“…However, S Protein seems to be the key determinant of evolution, transmission, and virulence of SARS-CoV-2. (23) Coronavirus entry into host cells is mediated, by the transmembrane spike (S) glycoprotein, that forms homotrimers protruding from the viral surface. (24) This protein comprises two functional subunits, responsible for binding to the host cell receptor (S1subunit), and fusion of the viral and cellular membranes (S2 subunit).…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Biochemistry, Transmission, Clinical Manifestations, and Prevention

Rao¹

2020

IJBM

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The first human case of COVID-19, caused by the novel coronavirus, was reported by health officials in the city of Wuhan, China, in December of 2019. The virus was identified as a novel coronavirus in early January 2020, and its genetic sequence was shared publicly on January 11, 2020. The novel virus, previously called 2019-novel coronavirus (2019-nCoV), is currently designated as the severe respiratory syndrome coronavirus-2 (SARS-CoV-2). On January 23, Wuhan was locked down, and the World Health Organization (WHO) declared a “public health emergency of international concern.” The viral genome of SARS-CoV-2 is around 29.8 kilobase, containing six major open reading frames. The most common clinical symptoms were fever, cough, fatigue, shortness of breath, dyspnea, muscle ache, headache, chest pain, vomiting, sore throat, and sputum production. The main mode of transmission is through respiratory particles. The incubation period is 3 to 7 days. Both asymptomatic and symptomatic patients seem to be infectious. Spike (S) proteins of SARS-CoV-2 seem to have a 10- to 20-fold higher affinity to the human angiotensin enzyme 2 (ACE2) receptor than that of SARS-CoV. The high affinity of S protein to theACE2 receptor, and the additional advantages offered by the transfection facilitators Furin and Neutropilin-1, likely, contributes to the rapid spreading of this novel virus. Since these receptors are highly expressed on a variety of cells, including vascular endothelial cells and adipose tissue, individuals with compromised function of these tissues drive greater infection and severity in patients with COVID-19. Global health experts estimate that one in five individuals worldwide could be at risk for severe COVID-19, due to underlying health conditions. There is a great need for a rapid, specific, cost-effective test for monitoring the infected individuals. Even though a 15- minute, antigen test was made available by Abbott recently, it seems that the schools, colleges, and business establishments lack the ability to use these tests effectively to keep their businesses open safely. Management of the infected individuals seems to be based on clinical symptoms that manifest as the disease progresses. The US Food & Drug Administration (FDA), has created a special emergency program for possible therapies, the Coronavirus Treatment Acceleration Program (CTAP). The program uses every available method to move new and emerging treatments as quickly as possible, keeping in mind the safety and efficacy of such therapies. According to the WHO report, there are currently more than 150 COVID-19 vaccine candidates under development. Several vaccines are in Phase 3 clinical trials. In an unprecedented effort, one of the experimental monoclonal antibody cocktails of Regeneron was used for therapeutic purposes when the US president was tested positive for COVID-19. There are no drugs or other therapeutics approved by the US FDA to prevent or treat COVID-19. The National Institutes of Health (NIH) have published interim guidelines for the medical management of COVID-19. In the absence of a cure, the only choice we all have is to follow the best practices recommended by the public health experts—use of face masks (coverings), frequent hand washing with soap, contact tracing of infected individuals, and quarantining COVID-19 positive individuals, till they are free of the highly infectious virus.

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“…Also, genomic surveillance of SARS-CoV-2 has been used to determine the correlation of these mutations to virulence diversity and their implications on reinfection, immunity, and vaccines development . 34 SARS-CoV-2 mutation data might provide valuable insights for the development of efficient vaccines, antivirals and laboratory test assays and protocols. Efforts are being made all over the world to control the spread of COVID-19 and most importantly, to develop a potent vaccine.…”

Section: Genomic Organization Of Sars-cov-2mentioning

confidence: 99%

Leveraging on the genomics and immunopathology of SARS-CoV-2 for vaccines development: prospects and challenges

Abdullahi

Emeribe

Adekola

et al. 2020

Human Vaccines & Immunotherapeutics

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The incidence and case-fatality rates (CFRs) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, the etiological agent for Coronavirus Disease 2019 (COVID-19), have been rising unabated. Even though the entire world has been implementing infection prevention and control measures, the pandemic continues to spread. It has been widely accepted that preventive vaccination strategies are the public health measures for countering this pandemic. This study critically reviews the latest scientific advancement in genomics, replication pattern, pathogenesis, and immunopathology of SARS-CoV-2 infection and how these concepts could be used in the development of vaccines. We also offer a detailed discussion on the anticipated potency, efficacy, safety, and pharmaco-economic issues that are and will be associated with candidate COVID-19 vaccines.

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Implications of SARS-CoV-2 genetic diversity and mutations on pathogenicity of the COVID-19 and biomedical interventions

Cited by 52 publications

References 38 publications

Mutation Landscape of SARS COV2 in Africa

Mutation Landscape of SARS COV2 in Africa

SARS-CoV-2 Biochemistry, Transmission, Clinical Manifestations, and Prevention

Leveraging on the genomics and immunopathology of SARS-CoV-2 for vaccines development: prospects and challenges

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